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A platform for the discovery of new macrolide antibiotics

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Seiple, Ian B., Zhang, Ziyang, Jakubec, Pavol, Langlois-Mercier, Audrey, Wright, Peter M., Hog, Daniel T., Yabu, Kazuo, Allu, Senkara Rao, Fukuzaki, Takehiro, Carlsen, Peter N., Kitamura, Yoshiaki, Zhou, Xiang, Condakes, Matthew L., Szczypiński, Filip T., Green, William D., Myers, Andrew G.·2016·Nature
DOI 10.1038/nature17967
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Abstract

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

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Metadata

Authors
Seiple, I. B., Zhang, Z., Jakubec, P., Langlois-Mercier, A., Wright, P. M., Hog, D. T., Yabu, K., Allu, S. R., Fukuzaki, T., Carlsen, P. N., Kitamura, Y., Zhou, X., Condakes, M. L., Szczypiński, F. T., Green, W. D., & Myers, A. G.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2016-05
Volume
533
Issue
7603
Pages
338-345
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature17967
OpenAlex
W2398757352
Cited by
351
References
0
FWCI
19.16
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: A platform for the discovery of new macrolide antibiotics. https://app.cochat.ai/papers/10.1038/nature17967
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Seiple, I. B., Zhang, Z., Jakubec, P., Langlois-Mercier, A., Wright, P. M., Hog, D. T., Yabu, K., Allu, S. R., Fukuzaki, T., Carlsen, P. N., Kitamura, Y., Zhou, X., Condakes, M. L., Szczypiński, F. T., Green, W. D., & Myers, A. G. (2016). A platform for the discovery of new macrolide antibiotics. Nature. https://doi.org/10.1038/nature17967

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